1. Investigation of Fascin1, a Marker of Mature Dendritic Cells, Reveals a New Role for IL-6 Signaling in CCR7-Mediated Chemotaxis.
- Author
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Matsumura F, Polz R, Singh S, Matsumura A, Scheller J, and Yamashiro S
- Subjects
- Animals, Antibodies, Blocking pharmacology, Antigens, Differentiation genetics, Cell Differentiation, Cells, Cultured, Chemotaxis, Gene Expression Regulation, Mice, Mice, Knockout, Microfilament Proteins genetics, Receptors, Interleukin-6 genetics, Receptors, Interleukin-6 immunology, Receptors, Interleukin-6 metabolism, Receptors, Odorant genetics, Signal Transduction, Antigens, Differentiation metabolism, Dendritic Cells immunology, Interleukin-6 metabolism, Microfilament Proteins metabolism, Receptors, CCR7 metabolism, Receptors, Odorant metabolism
- Abstract
Migration of mature dendritic cells (DCs) to lymph nodes is critical for the initiation of adaptive immunity. CCR7, a G-protein-coupled receptor for CCL19/21 chemokines, is known to be essential for chemotaxis of mature DCs, but the molecular mechanism linking inflammation to chemotaxis remains unclear. We previously demonstrated that fascin1, an actin-bundling protein, increases chemotaxis of mature mouse DCs. In this article, we demonstrated that fascin1 enhanced IL-6 secretion and signaling of mature mouse DCs. Furthermore, we demonstrated that IL-6 signaling is required for chemotaxis. Blockage of IL-6 signaling in wild-type DCs with an anti-IL-6 receptor α (IL-6Rα) Ab inhibited chemotaxis toward CCL19. Likewise, knockout of IL-6Rα inhibited chemotaxis of bone marrow-derived DCs. The addition of soluble IL-6Rα and IL-6 rescued chemotaxis of IL-6Rα knockout bone marrow-derived DCs, underscoring the role of IL-6 signaling in chemotaxis. We found that IL-6 signaling is required for internalization of CCR7, the initial step of CCR7 recycling. CCR7 recycling is essential for CCR7-mediated chemotaxis, explaining why IL-6 signaling is required for chemotaxis of mature DCs. Our results have identified IL-6 signaling as a new regulatory pathway for CCR7/CCL19-mediated chemotaxis and suggest that rapid migration of mature DCs to lymph nodes depends on inflammation-associated IL-6 signaling., (Copyright © 2021 by The American Association of Immunologists, Inc.)
- Published
- 2021
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